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Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice
Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly re...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599671/ https://www.ncbi.nlm.nih.gov/pubmed/26251044 http://dx.doi.org/10.1093/hmg/ddv323 |
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author | Pelosi, Laura Berardinelli, Maria Grazia Forcina, Laura Spelta, Elisa Rizzuto, Emanuele Nicoletti, Carmine Camilli, Carlotta Testa, Erika Catizone, Angela De Benedetti, Fabrizio Musarò, Antonio |
author_facet | Pelosi, Laura Berardinelli, Maria Grazia Forcina, Laura Spelta, Elisa Rizzuto, Emanuele Nicoletti, Carmine Camilli, Carlotta Testa, Erika Catizone, Angela De Benedetti, Fabrizio Musarò, Antonio |
author_sort | Pelosi, Laura |
collection | PubMed |
description | Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly regenerates and regains structural and functional integrity. The basis for the mild effects observed in mice compared with the lethal consequences in humans remains unknown. In this study, we provide evidence that interleukin-6 (IL-6) is causally linked to the pathogenesis of muscular dystrophy. We report that forced expression of IL-6, in the adult mdx mice, recapitulates the severe phenotypic characteristics of DMD in humans. Increased levels of IL-6 exacerbate the dystrophic muscle phenotype, sustaining inflammatory response and repeated cycles of muscle degeneration and regeneration, leading to exhaustion of satellite cells. The mdx/IL6 mouse closely approximates the human disease and more faithfully recapitulates the disease progression in humans. This study promises to significantly advance our understanding of the pathogenic mechanisms that lead to DMD. |
format | Online Article Text |
id | pubmed-4599671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-45996712015-10-14 Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice Pelosi, Laura Berardinelli, Maria Grazia Forcina, Laura Spelta, Elisa Rizzuto, Emanuele Nicoletti, Carmine Camilli, Carlotta Testa, Erika Catizone, Angela De Benedetti, Fabrizio Musarò, Antonio Hum Mol Genet Articles Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly regenerates and regains structural and functional integrity. The basis for the mild effects observed in mice compared with the lethal consequences in humans remains unknown. In this study, we provide evidence that interleukin-6 (IL-6) is causally linked to the pathogenesis of muscular dystrophy. We report that forced expression of IL-6, in the adult mdx mice, recapitulates the severe phenotypic characteristics of DMD in humans. Increased levels of IL-6 exacerbate the dystrophic muscle phenotype, sustaining inflammatory response and repeated cycles of muscle degeneration and regeneration, leading to exhaustion of satellite cells. The mdx/IL6 mouse closely approximates the human disease and more faithfully recapitulates the disease progression in humans. This study promises to significantly advance our understanding of the pathogenic mechanisms that lead to DMD. Oxford University Press 2015-11-01 2015-08-06 /pmc/articles/PMC4599671/ /pubmed/26251044 http://dx.doi.org/10.1093/hmg/ddv323 Text en © The Author 2015. Published by Oxford University Press http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Pelosi, Laura Berardinelli, Maria Grazia Forcina, Laura Spelta, Elisa Rizzuto, Emanuele Nicoletti, Carmine Camilli, Carlotta Testa, Erika Catizone, Angela De Benedetti, Fabrizio Musarò, Antonio Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice |
title | Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice |
title_full | Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice |
title_fullStr | Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice |
title_full_unstemmed | Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice |
title_short | Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice |
title_sort | increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599671/ https://www.ncbi.nlm.nih.gov/pubmed/26251044 http://dx.doi.org/10.1093/hmg/ddv323 |
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